| 3. Round | 30/01/2022 | Independiente Medellín | - | Deportivo Cali | 2:0 | ||||
| 5. Round | 08/02/2022 | Independiente Medellín | - | Cortuluá | 3:1 | ||||
| 7. Round | 17/02/2022 | Independiente Medellín | - | Atlético Junior | 2:0 | ||||
| 8. Round | 19/02/2022 | Santa Fe | - | Independiente Medellín | 1:0 | ||||
| 9. Round | 02/03/2022 | Independiente Medellín | - | Águilas Doradas | 4:0 | ||||
| 11. Round | 20/03/2022 | América de Cali | - | Independiente Medellín | 1:3 | ||||
| 12. Round | 24/03/2022 | Independiente Medellín | - | Millonarios | 1:0 |  |
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| 13. Round | 27/03/2022 | Deportivo Pereira | - | Independiente Medellín | 1:1 | ||||
| 14. Round | 02/04/2022 | Independiente Medellín | - | Envigado FC | 2:1 | ||||
| 15. Round | 11/04/2022 | Alianza Petrolera | - | Independiente Medellín | 1:1 | ||||
| 17. Round | 23/04/2022 | Atlético Bucaramanga | - | Independiente Medellín | 2:3 | ||||
| 18. Round | 30/04/2022 | Independiente Medellín | - | Atlético Nacional | 0:0 | |
Uruguay